Synthesis and interaction with human serum albumin of the first 3,18-disubstituted derivative of bilirubin
作者:Leoni Painter、Margaret M. Harding、Philip J. Beeby
DOI:10.1039/a803429j
日期:——
Addition of excess (>500 equiv.) of p-fluorothiophenol to bilirubin in the presence of toluene-p-sulfonic acid catalyst afforded 3,18-didevinyl-3,18-bis[2-(p-fluorothiophenyl)ethyl] bilirubin 2 from anti-Markovnikov addition to both the exo and endo vinyl groups of bilirubin. Toluene-p-sulfonic acid is not essential as p-fluorothiophenol acts as the acid and nucleophile in the reaction. In contrast, in the presence of toluene-p-sulfonic acid, regioselective Markovnikov addition of thioacetic S-acid to the exo vinyl group occurs, in agreement with previous studies of the addition of a range of oxygen and sulfur nucleophiles to bilirubin (P. Manitto and D. Monti, Experientia, 1973, 29, 137). Binding of 2 to human serum albumin was measured by circular dichroism. The two bulky p-fluorothiophenyl groups do not appear to impede interaction with the protein. This result supports a model in which the reactive methylene bridge of bilirubin, that connects rings B and C, points into the binding pocket of human serum albumin.
在甲苯-对磺酸催化剂存在下,将过量(大于 500 等份)的对氟苯硫酚加到胆红素上,通过对胆红素的外乙烯基和内乙烯基进行反马尔科夫尼科夫加成反应,得到 3,18-二乙烯基-3,18-双[2-(对氟噻吩)乙基]胆红素 2。由于对氟苯硫酚在反应中既是酸又是亲核体,因此对氟苯硫酚不是必不可少的。相反,在甲苯对磺酸存在的情况下,硫代乙酸 S-酸与外乙烯基发生区域选择性马尔科夫尼科夫加成反应,这与之前对一系列氧和硫亲核物与胆红素加成反应的研究结果一致(P. Manitto 和 D. Monti,Experientia,1973,29,137)。通过圆二色性测量了 2 与人血清白蛋白的结合。两个笨重的对氟噻吩基团似乎并不妨碍与蛋白质的相互作用。这一结果支持这样一种模型,即连接环 B 和环 C 的胆红素反应性亚甲基桥指向人血清白蛋白的结合袋。